Project Summary Primary prevention of HPV-related urogenital and oropharyngeal cancers could significantly reduce morbidity, mortality, and healthcare costs associated with these commonly occurring cancers. The vaccine targeting oncogenic strains of the human papilloma virus (HPV) can prevent HPV-related cancers if given to girls and boys before exposure to these sexually transmitted viruses. Yet, in the United States (U.S.), more than 10 years after introduction of the vaccine, fewer than half of the target population is vaccinated. The objective of this application is to evaluate the effectiveness of an implementation strategy (the intervention) to improve optimal use of the HPV vaccine. Optimal use requires completion of the 2-dose series before sexual debut. To this end, national recommendations from the Centers for Disease Control and Prevention (CDC) are to complete the 2-dose HPV vaccine series by age 13. The theory-based, multi- component intervention was developed in collaboration with primary care providers and includes: 1) an educational video to increase the provider?s knowledge about guideline recommendations and patient and practice benefits of vaccination by age 13; 2) audit and feedback of vaccine coverage to increase motivation to engage in practice change; 3) a communication strategy to improve the provider?s communication skills and their self-efficacy to address parental hesitation; and 4) practice facilitation to support practice change to develop a sustainable HPV vaccine delivery system. The intervention will be delivered through a series of brief practice visits with the facilitator that occur every 1-4 weeks over 2 years. In a pilot study, the intervention was well-accepted and resulted in a clinically meaningful improvement in vaccine initiation of 19 percentage points over 15-months. This promising intervention will be evaluated in a cluster-randomized trial in 20 primary care pediatric practices in Missouri, a state with low HPV vaccine coverage. Study objectives are to 1) determine if the intervention will increase initiation (primary outcome) and completion (secondary outcome) of the 2-dose HPV vaccine series for preteens before their 13th birthday; 2) determine if provider motivation and improved communication skills mediate the effectiveness of the intervention; and 3) assess factors important for scaling including fidelity, acceptance by primary care providers and parents, and cost. Vaccine use in preteens will be assessed at baseline, at 24 months to assess effectiveness, and at 36 months to assess if change is sustained. For the primary analyses, aggregates of patient-level data will be used to estimate provider behavior, extracting data from the practices? electronic medical record.